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Biomedical subjects

D F Nutting

Publications and source records attributed to D F Nutting.

29 records · Page 2Linked to original sources
PubMed1981

Parathyroid ablation in dystrophic hamsters. Effects on Ca content and histology of heart, diaphragm, and rectus femoris.

Cumulative evidence indicates that there is an increased accumulation of calcium in dystrophic muscle and that this may have a pathophysiological role in the progression of the dystrophic process. The accumulation may be related to a defect of the plasma membrane. Because parathyroid hormone (PTH) stimulates calcium influx into the cytosol, the chronic effects of surgical ablation of the parathyroid glands on muscle Ca, Mg, protein synthesis, and histology, as well as plasma creatine phosphokinase (CPK), Ca, and Mg, were studied in normal and dystrophic (BIO 14.6) hamsters. Thyroparathyroidectomized (TPTX) hamsters receiving replacement doses of l-thyroxine were killed at age 90 d, 55 d after TPTX. In intact dystrophic hamsters, the Ca content in the heart was 20 times higher than in normal animals and was reduced by half in TPTX dystrophic hamsters. Similar results were observed in diaphragm and rectus femoris. No abnormalities in Mg content were observed in intact or TPTX dystrophic hamsters. Ether-extractable fat of the heart and diaphragm was reduced in dystrophic hamsters and was not modified by TPTX. Protein synthesis was enhanced in the diaphragm of dystrophic hamsters but was not changed by TPTX. The concentration of CPK in plasma was elevated in dystrophic hamsters and fell significantly after TPTX. In the latter animals, microscopic examination of the heart showed lesser signs of dystrophy, particularly in the degree of fibrosis. To determine the degree of dystrophy at the age when TPTX was performed, identical analyses were made in 35-d-old hamsters. Definitive histological signs of dystrophy were observed, and although the Ca content in heart, diaphragm, and rectus femoris was elevated, the values were lower than in 90-d-old intact and TPTX dystrophic hamsters. This indicates that chronic TPTX in dystrophic hamsters reduces, but does not arrest, the dystrophic process. In normal hamsters, a 50% reduction in plasma Ca concentration was observed 6 h after TPTX; 55 d after TPTX, however, plasma Ca was within normal limits in both normal and dystrophic hamsters. No parathyroid tissue was observed in serial sections of the trachea and adjacent tissues in TPTX animals. This suggests that in chronically TPTX hamsters fed a standard laboratory diet, plasma Ca can be maintained by mechanisms independent of parathyroid function. THE DATA INDICATE THAT IN DYSTROPHIC HAMSTERS TPTX CAUSES A MARKED REDUCTION IN: (a) muscle Ca accumulation, (b) levels of plasma CPK and, (c) intensity of histological changes in the heart. These changes were independent of the levels of plasma Ca and were not observed in normal hamsters. We conclude that PTH accentuates the dystrophic process, probably by enhancing the already increased Ca flux into muscle (apparently caused by defective sarcolemma). We postulate that normal secretion of PTH may have a deleterious effect in congenital or acquired conditions associated with altered plasma membranes.

Adipose Tissue↗
PubMed1979

In vitro effects of fatty acids on the actions of serum on rat and pig cartilage.

It has been reported that fatty acids preferentially inhibit serum-stimulated incorporation of sulfate by embryonic chick cartilage, suggesting that they may interfere with the effects of a proposed mediator (serum somatomedin) of the actions of growth hormone (GH). This was studied further in mammalian cartilage. Butyrate and octanoate at concentrations of 0.5 to 5 mM produced a concentration-dependent inhibition of both basal and serum-stimulated sulfate and thymidine incorporation by costal cartilage from hypophysectomized rats. Butyrate also inhibited basal and serum-stimulated sulfate incorporation in cartilage from normal pigs and normal sucklings rats. In all 3 test systems, oleate (0.2--5 mM) bound to serum albumin (4 g/dl) was ineffective. There was no evidence that fatty acids preferentially inhibited the stimulation of sulfate incorporation produced by serum.

Animals↗
PubMed1976

Ontogeny of sensitivity to growth hormone in rat diaphragm muscle.

In order to delineate the ages of onset and decline in sensitivity to growth hormone (GH) in rats, the ability of ovine GH in vitro to stimulate amino acid uptake and protein synthesis was studied in diaphragm muscle. GH (25 mug/ml) produced a significant, but small (12-17%), stimulation of alpha-aminoisobutyric acid (AIB, 1 mM) uptake in diaphragms from fed intact rats 7-24 days old, but not from 21-day fetuses or from fed rats 4, 30, 50, 100, or 130 days old. When intact rats were fasted for 24 h, both the magnitude and consistency of the responses to GH increased considerably. In fasted rats, GH significantly stimulated AIB transport by 10,29, 77,111, and 58% at ages 4, 7, 11, 15, and 23 days, respectively; GH was not effective at age 3 or 30 days. At age 15 days, 0.5 mug/ml GH stimulated AIB transport by 96%. GH (25 or 0.5 mug/ml) significantly increased leucine incorporation into protein at age 15 days in fasted intact rats. When rats were hypophysectomized at age 28, 47, or 98 days and tested 2-3 days later, the basal rate of protein synthesis fell, but the basal rate of AIB transport did not; however, GH now stimulated both AIB uptake and amino acid incorporation into protein. These results suggest that rat diaphragm muscle first becomes sensitive to GH at about age 4-7 days (AIB transport), but that further development may be necessary for the anabolic action of the hormone (protein synthesis) to be seen. Stimulation of AIB uptake is maximal about 15 days after birth. Thereafter, diaphragm muscles from normal rats becomes progressively more refractory to the acute stimulatory effects of GH on transport processes. Hypphysectomy of rats 30 days old or more leads to the re-establishment of GH-responsiveness by the AIB transport system. This cannot be attributed merely to a lowering of the basal transport rate; rather hypophysectomy appears to result in the loss of an inhibitor of growth hormone's acute stimulatory actions on transport processes. Previous work suggests that this refractory state is produced in normal rats by occasional surges of endogenous growth hormone. The dominance of the refractory state appears about the time of weaning. This may protect the weaned rat, whose diet is more variable than it is during the suckling period, from periodic depletion of amino acids and glucose from the plasma in response to intermittent surges of GH, thereby allowing GH to produce a sustained stimulation of protein synthesis and growth.

Age Factors↗
PubMed1976

Effects of growth hormone, thyroxine, and age on diaphragm muscle from dwarf mice.

The ability of GH in vitro to stimulate leucine incorporation into protein and the uptake of 2-aminoisobutyric acid (AIB) and 3-O-methyl-glucose (3-OMG) was studied in diaphragm muscle from dwarf (dw/dw) mice. Ovine GH (25 mug/ml) significantly enhanced the rate of protein synthesis in muscle from untreated dwarfs. In contrast, GH usually failed to stimulate transport, although occasionally a small increase in AIB uptake was seen. Insulin (50 muU/ml) readily stimulated both AIB transport and protein synthesis in muscle from untreated dwarfs. Dwarfs were treated for 4 days with thyroxine (T4) (0.3-5 mug/day) or 3,5,3'-triiodo thyronine (T3) (0.1 mug/day). This enhanced the responsiveness of the transport systems to GH and seemed to increase the basal transport rates for AIB and 3-OMG. After the T4-treatment 0.75 mug/ml GH stimulated AIB transport in mice aged 15 weeks; 25 mug/ml GH stimulated AIB transport in dwarfs aged 5 weeks-1 yr. and leucine incorporation into protein in dwarfs aged 5 weeks-2 yr. This last result suggests that response to GH does not cease merely due to increasing age. Synergism by T3/T4 was not permanent, and the maximum response to GH occurred 1 week after the last injection of T4. The possible mechanisms whereby thyroid hormones enhance responsiveness of the transport systems to GH are discussed.

Age Factors↗